Alpha-synuclein antibodies and uses thereof

Abstract

The invention describes antibodies having a high affinity for aggregated forms of α-synuclein and a low affinity for monomeric forms of α-synuclein. The antibodies are useful in the diagnosis of neurodegenerative diseases.

1 . An antibody or fragment thereof having high affinity for α-synuclein aggregates and low affinity binding for synuclein monomers. 
     
     
         2 . An antibody or fragment thereof according to  claim 1  wherein the α-synuclein aggregates comprise protofibrils and/or soluble oligomers of α-synuclein. 
     
     
         3 . An antibody or fragment thereof according to  claim 1  wherein the α-synuclein aggregates comprise α-synuclein fibrils. 
     
     
         4 . An antibody or fragment thereof according to  claim 1  wherein the antibody or fragment thereof has a dissociation constant, Kd, of less than 10 −7  M for human α-synuclein aggregates. 
     
     
         5 . An antibody or fragment thereof according to  claim 1  wherein the antibody or fragment thereof has a dissociation constant, Kd, of more than 10 −5  M for monomeric α-synuclein. 
     
     
         6 . Antibody or fragment thereof according to  claim 1  wherein the antibody has a higher affinity for α-synucleins fibrils than for oligomeric forms of α-synucleins. 
     
     
         7 . An antibody or fragment thereof according to  claim 1  wherein the antibody or fragment thereof binds to an epitope comprising a C-terminal region of α-synuclein. 
     
     
         8 . An antibody or fragment thereof according to  claim 1  wherein the antibody or fragment thereof is a confirmational antibody. 
     
     
         9 . An antibody or fragment thereof according to  claim 1  wherein the antibody or fragment thereof do not recognise a linear epitope of α-synuclein. 
     
     
         10 . An antibody or fragment thereof according to  claim 1  wherein the antibody is a monoclonal antibody. 
     
     
         11 . A pharmaceutical composition comprising an antibody or fragment according to  claim 1  and a pharmaceutically acceptable diluent or carrier. 
     
     
         12 . An antibody or fragment according to  claim 1  for use as a medicament. 
     
     
         13 . A method for preventing or treating a neurodegenerative disorder with α-synuclein pathology in an individual comprising administration of an antibody or fragment according to  claim 1  to the individual. 
     
     
         14 . A method according to  claim 13 , wherein the neurodegenerative disorder is Parkinson's disease, dementia with Lewy Bodies, Alzheimer's disease, multiple system atrophy, psychosis, schizophrenia or Creutzfeldt-Jakob disease. 
     
     
         15 . A test kit for use in a method of determining whether or not an individual has a neurodegenerative disease comprising an antibody or fragment thereof according to  claim 1 . 
     
     
         16 . A method of detecting α-synuclein fibrils and aggregates comprising the steps of
 adding the antibody or fragment according to  claim 1  to a biological sample, and 
 detecting the presence of a complex formed between α-synuclein fibrils and/or aggregates and the antibody or fragment. 
 
     
     
         17 . A method for diagnosing a neurodegenerative disease associated with α-synuclein comprising:
 adding the antibody or fragment according to  claim 1  to a biological sample from a subject, and 
 detecting the presence or absence of a complex formed between α-synuclein aggregates and the antibody or fragment. 
 
     
     
         18 . An antibody or fragment according to  claim 1  for use as an imaging agent. 
     
     
         19 . A method for imaging α-synuclein aggregates comprising
 administering the antibody or fragment according to  claim 1  to an individual, and 
 detecting the antibody. 
 
     
     
         20 . The method according to  claim 19  wherein the antibody comprises a detectable label.